A5037694488- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- ATP Synthase and ATPases Research
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- Viral gastroenteritis research and epidemiology
- Genetic Neurodegenerative Diseases
- SARS-CoV-2 and COVID-19 Research
- Animal Virus Infections Studies
- Photosynthetic Processes and Mechanisms
- Plant Reproductive Biology
- Plant Molecular Biology Research
- Fungal and yeast genetics research
- Polysaccharides and Plant Cell Walls
- Cell death mechanisms and regulation
- Diabetes and associated disorders
- Cancer therapeutics and mechanisms
- Endoplasmic Reticulum Stress and Disease
- Ubiquitin and proteasome pathways
- Liver Diseases and Immunity
- Peptidase Inhibition and Analysis
- Lipid metabolism and biosynthesis
- Bacterial Genetics and Biotechnology
Icosagen (Estonia)
2022-2024
University of Tartu
2006-2023
Radboud University Nijmegen
2012-2017
Radboud University Medical Center
2012-2017
Newcastle University
2015
Tampere University
2013
University of Kaiserslautern
2008
Maintenance of topological homeostasis is vital for gene expression and genome replication in all organisms. Similar to other circular genomes, also mitochondrial DNA (mtDNA) known exist various different forms, although their functional significance remains unknown. We report here that both type II topoisomerases Top2α Top2β are present mammalian mitochondria, with especially regulating the supercoiling state mtDNA. Loss or its inhibition by ciprofloxacin results accumulation positively...
Abstract The helicase Twinkle is indispensable for mtDNA replication in nucleoids. Previously, we showed that tightly membrane-associated even the absence of mtDNA, which suggests part a membrane-attached platform. Here show this platform cholesterol-rich membrane structure. We fractionated mitochondrial preparations on flotation gradients and nucleoids accumulate at top gradient. This fraction was shown to be highly enriched cholesterol, lipid otherwise low abundant mitochondria. In...
Plant cells can be distinguished from animal by their cell walls and high-turgor pressure. Although changes in turgor the stiffness of seem coordinated, we know little about mechanism responsible for coordination. Evidence has accumulated that plants, like yeast, have a dedicated wall integrity maintenance mechanism. It monitors functional maintains through adaptive responses induced damage arising during growth, development, interactions with environment. These include osmosensitive...
Mitochondrial DNA (mtDNA) is organized in discrete protein–DNA complexes, nucleoids, that are usually considered to be mitochondrial-inner-membrane associated. Here we addressed the association of replication factors with nucleoids and show endogenous mtDNA helicase Twinkle single-stranded DNA-binding protein, mtSSB, co-localize only a subset nucleoids. Using nucleotide analogs identify replicating situ, fraction label-positive Twinkle/mtSSB positive, highest shortest labeling-pulse. In...
Abstract Many metabolic reactions in the endoplasmic reticulum (ER) require high levels of energy form ATP, which is important for cell viability. Here, we report on an adenine nucleotide transporter residing ER membranes Arabidopsis thaliana (ER-ANT1). Functional integration ER-ANT1 cytoplasmic membrane intact Escherichia coli cells reveals a specificity ATP/ADP antiport. Immunodetection transgenic ER-ANT1-C-MYC-tag plants and immunogold labeling wild-type pollen grain tissue using...
The mitochondrial replicative helicase Twinkle is involved in strand separation at the replication fork of DNA (mtDNA). malfunction associated with rare diseases that include late onset myopathies, neuromuscular disorders and fatal infantile mtDNA depletion syndrome. We examined its 3D structure by electron microscopy (EM) small angle X-ray scattering (SAXS) built corresponding atomic models, which gave insight into first molecular architecture a full-length SF4 includes an N-terminal...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to impose a serious burden on health systems globally. Despite worldwide vaccination, social distancing and wearing masks, the spread of virus is ongoing. One mechanisms by which neutralizing antibodies (NAbs) block entry into cells encompasses interaction inhibition between cell surface receptor angiotensin-converting enzyme (ACE2) spike (S) protein SARS-CoV-2. SARS-CoV-2-specific NAb development can be induced in blood...
ABSTRACT The Fe(II) and 2-oxoglutarate-dependent oxygenase Alkb homologue 1 (Alkbh1) has been shown to act on a wide range of substrates, like DNA, tRNA histones. Thereby different enzymatic activities have identified including, among others, demethylation N3-methylcytosine (m3C) in RNA- single-stranded DNA oligonucleotides, N1-methyladenosine (m1A) or formation 5-formyl cytosine (f5C) tRNA. In accordance with the Alkbh1 also proposed reside distinct cellular compartments human mouse cells,...
Mitochondria of eukaryotic organisms contain populations DNA molecules that are packed into higher-order structures called mitochondrial nucleoids (mt-nucleoids). In Saccharomyces cerevisiae, the compaction (mtDNA) mt-nucleoids is mediated primarily by high-mobility group (HMG) box-containing protein Abf2, which an important player in stabilization and metabolism mtDNA. Although it evident analogous proteins must exist other yeast species, apparently fast divergence rate has precluded their...
The evidence that pan-Bcl-2 or Bcl-xL-specific inhibitors prematurely kill virus-infected RNA/DNA-transfected cells provides rationale for investigating these apoptotic inducers further. We hypothesized not only invasive RNA DNA (biological factors) but also DNA/RNA-damaging chemical physical factors could trigger apoptosis have been sensitized with agents; Methods: tested and plus inhibitor A-1155463 in of various origins the small roundworms (C. elegans); Results: show combination a along...
The compaction of mitochondrial DNA (mtDNA) is regulated by architectural HMG-box proteins whose limited cross-species similarity suggests diverse underlying mechanisms. Viability Candida albicans, a human antibiotic-resistant mucosal pathogen, compromised altering mtDNA regulators. Among them, there the maintenance factor Gcf1p, which differs in sequence and structure from its Saccharomyces cerevisiae counterparts, TFAM Abf2p. Our crystallographic, biophysical, biochemical computational...
The mechanistic details of mtDNA maintenance in petite-negative yeasts have remained largely unexplored. We report here that the DNA helicase Hmi1p plays a crucial role stability Candida albicans. Like its counterpart Saccharomyces cerevisiae, C. albicans (CaHmi1p) contains C-terminal mitochondrial targeting signal is functional both organisms. Biochemical analysis demonstrates CaHmi1p protein possessing ATP-dependent 3'-5' DNA-unwinding activity. Deletion HMI1 alleles does not lead to...
The helicase Twinkle is indispensable for mtDNA replication in nucleoids. Previously, we showed that tightly membrane-associated even the absence of mtDNA, which suggests part a membrane-attached platform. Here show this platform cholesterol-rich membrane structure. We fractionated mitochondrial preparations on flotation gradients and nucleoids accumulate at top gradient. This fraction was shown to be highly enriched cholesterol, lipid otherwise low abundant mitochondria. In contrast, more...
ABSTRACT The evidence that pan-Bcl-2 or Bcl-xL-specific inhibitors prematurely kill virus-infected RNA/DNA-transfected cells provides rationale for investigating these apoptotic inducers further. Here, we show agent A-1155463 kills of different origins and the small roundworms ( C. elegans ), when combined with DNA-damaging 4-nitroquinoline-1-oxide (4NQO). synergistic effect 4NQO-A-1155463 combination was p53-dependent, associated release Bad Bax from Bcl-xL, which triggered mitochondrial...
The correct organization of mitochondrial DNA (mtDNA) in nucleoids and the contacts mitochondria with ER play an important role maintaining genome distribution within cell. Mitochondria-associated membranes (MAMs) consist interacting proteins lipids located outer membrane membrane, forming a platform for inner membrane-associated replication factory as well connecting division machinery. We show here that knockdown core component nucleoids, TFAM, causes changes nucleoid populations, which...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread in the population. We recently reported production of bovine colostrum-derived antibodies that can neutralize virus. These have been formulated into a nasal spray. The immunoglobulin preparation is capable blocking interaction trimeric spike protein (Tri S) SARS-CoV-2 with cellular receptor angiotensin-converting enzyme (ACE2), entry pseudovirus carrying Tri S ACE2 over-expressing human embryonic kidney (HEK)...
Abstract Background Nonalcoholic fatty liver disease (NAFLD) is on the rise in Western industrialized countries and associated comorbidities like e.g. cirrhosis are a major cause of transplantations USA. In NAFLD, excess fat accumulated whereas this build-up not caused by alcohol. NASH (nonalcoholic steatohepatitis) NAFL liver) two forms NAFLD. represents stage which does exhibit signs inflammation or damage, while does. necessarily progress to damage. other hand may fibrosis lead with risk...
Abstract Plant cells can be distinguished from animal by their cell walls and high turgor pressure. Although changes in stiffness of seem coordinated, we know little about the mechanism responsible for coordination. Evidence has accumulated that plants, like yeast, have a dedicated wall integrity maintenance mechanism. This monitors functional maintains it through adaptive responses when damage occurs during growth, development, interactions with environment. The include...